Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence

Background: Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI. Methods: The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented. Results: The majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI. Conclusions: The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit. Clinical Trials Registration: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II)

Cost-Effectiveness Analysis of Bezlotoxumab Added to Standard of Care Versus Standard of Care Alone for the Prevention of Recurrent Clostridium difficile Infection in High-Risk Patients in Spain

Introduction Clostridium difficile infection (CDI) is the major cause of infectious nosocomial diarrhoea and is associated with considerable morbidity, mortality and economic impact. Bezlotoxumab administered in combination with standard of care (SoC) antibiotic therapy prevents recurrent CDI. This study assessed the cost-effectiveness of bezlotoxumab added to SoC, compared to SoC alone, to prevent the recurrence of CDI in high-risk patients from the Spanish National Health System perspective. Methods A Markov model was used to simulate the natural history of CDI over a lifetime horizon in five populations of patients at high risk of CDI recurrence according to MODIFY trials: (1) ≥ 65 years old; (2) severe CDI; (3) immunocompromised; (4) ≥ 1 CDI episode in the previous 6 months; and (5) ≥ 65 years old and with ≥ 1 CDI episode in the previous 6 months. The incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. Results In all patient populations (from 1 to 5), bezlotoxumab added to SoC reduced CDI recurrence compared to SoC alone by 26.4, 19.5, 21.2, 26.6 and 39.7%, respectively. The resulting ICERs for the respective subgroups were €12,724, €17,495, €9545, €7386, and €4378. The model parameters with highest impact on the ICER were recurrence rate (first), mortality, and utility values. The probability that bezlotoxumab was cost-effective at a willingness-to-pay threshold of €21,000/QALY was 85.5%, 54.1%, 86.0%, 94.5%, 99.6%, respectively. Conclusion The results suggest that bezlotoxumab added to SoC compared to SoC alone is a cost-effective treatment to prevent the recurrence of CDI in high-risk patients. The influence of changes in model parameters on DSA results was higher in patients  ≥ 65 years old, with severe CDI and immunocompromised. Additionally, PSA estimated that the probability of cost-effectiveness exceeded 85% in most subgroups

Enhancing professionalism - progressing the career development sector

Much has changed in the career development sector since the launch of the Careers Profession Task Force report, ‘Towards a Strong Careers Profession’ in 2010. The report made recommendations for enhancing the professionalism of the career sector including the establishment of an overarching professional body, new qualification levels and common professional standards. The Careers Profession Alliance (CPA) and then the Career Development Institute (CDI), launched in April 2013 have striven to facilitate the sector to be stronger and more cohesive by addressing these recommendations. This article explores what was needed, what has been achieved and plans for the future

Social Security Administration: Workloads, Resources, and Service Delivery

Some Members of Congress have expressed concern about whether the Social Security Administration (SSA) has adequate resources to manage its workloads. The agency has struggled to provide quality service to the public. Backlogs in the disability programs have caused widespread concern. SSA’s efforts to ensure the accuracy of benefit payments have declined. Many applicants and beneficiaries have experienced long waits at field offices and on the phone. SSA’s workloads are growing as the population increases, the baby boomers retire, the economic situation worsens, and the agency takes on new and more complex responsibilities. SSA’s primary workload is administering the Social Security and Supplemental Security Income (SSI) programs. In addition, SSA provides substantial administrative support to Medicare and other programs, and partners with the Department of Homeland Security in verifying employment eligibility. The resources SSA has to meet its growing workloads include funding, staff, infrastructure, and management. In recent years, SSA’s administrative funding has increased, but has generally fallen short of requests by the SSA Commissioner and the Bush Administration. SSA’s FY2008 appropriation was the first time that Congress appropriated at or above the President’s budget request in over ten years. SSA’s staffing levels have decreased overall and fluctuated among the specialized staff who manage key workloads; at the same time, SSA’s productivity has increased, according to agency measures. The agency has gradually modernized its technological infrastructure and made efforts to streamline its processes, but independent analysts have argued that these initiatives fall short of what is needed to meet SSA’s growing workloads. Congress could facilitate changes at SSA through the appropriations and oversight processes. Options for congressional action include changing the amount of SSA’s administrative expenses and how they are financed. For example, the Social Security Advisory Board (SSAB) has recommended that Congress increase funding for SSA’s administrative expenses, arguing that the agency does not have adequate resources. The board has also suggested excluding SSA’s administrative costs from discretionary spending caps. The Government Accountability Office (GAO) has recommended dedicating funds for program integrity. Congress could also use its oversight powers to encourage more effective management at SSA in areas such as implementing technological improvements, streamlining processes, and recruiting and retaining key staff. Congress could decide not to take any action. However, inaction would likely have consequences. As SSA’s workloads increase, it is unlikely that the agency would be able to reduce the backlogs in the disability programs, and possible that the backlogs would grow further, resulting in longer waits for potential beneficiaries. Managing growing workloads could also preclude efforts to maintain or increase the program integrity activities that are projected to save the Social Security and SSI programs money in the long run. Customer service problems could be difficult to address in the absence of additional staff or resources. Finally, SSA’s outdated computer systems pose security risks and are vulnerable to collapse, according to outside experts. This report provides an overview of SSA’s workloads, resources, and service delivery, as well as issues for Congress. It does not cover H.R. 1 and S.Amdt. 98, which are intended to provide a stimulus to the economy. For more information on that legislation, please see CRS Report R40188, Comparison of Social Security Provisions in the Stimulus Packages Proposed by the House of Representatives and Senate. This report will not be updated

Early vocabulary development in deaf native signers: a British Sign Language adaptation of the communicative development inventories

Background: There is a dearth of assessments of sign language development in young deaf children. This study gathered age-related scores from a sample of deaf native signing children using an adapted version of the MacArthur-Bates CDI (Fenson et al., 1994). Method: Parental reports on children’s receptive and expressive signing were collected longitudinally on 29 deaf native British Sign Language (BSL) users, aged 8–36 months, yielding 146 datasets. Results: A smooth upward growth curve was obtained for early vocabulary development and percentile scores were derived. In the main, receptive scores were in advance of expressive scores. No gender bias was observed. Correlational analysis identified factors associated with vocabulary development, including parental education and mothers’ training in BSL. Individual children’s profiles showed a range of development and some evidence of a growth spurt. Clinical and research issues relating to the measure are discussed. Conclusions: The study has developed a valid, reliable measure of vocabulary development in BSL. Further research is needed to investigate the relationship between vocabulary acquisition in native and non-native signers

Further education learners' prior experience of career education and guidance: A case study of Chesterfield College.

This article explores further education (FE) students' prior experiences of careers education. The research draws on and extends the limited literature that exists around career support in further education. A mixed methods case study was used to explore students' experience of careers work prior to attending Chesterfield College and to examine the implications of this for the college's provision of career support. Findings indicate that the majority of students had limited contact with careers workers prior to their arrival at the college and, in instances when they had contact, often had a negative preconception of this contact. These findings are discussed with reference to the college's careers education provision and the wider implications for the sector

Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel Australian hospitals in 2013: the Influenza Complications Alert Network

The National Influenza Program aims to reduce serious morbidity and mortality from influenza by providing public funding for vaccination to at-risk groups. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 14 sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with confirmed influenza, estimates vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2013 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals, with influenza confirmed by nucleic acid testing. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 5 April to 31 October 2012, 631 patients were admitted with confirmed influenza at the 14 FluCAN sentinel hospitals. Of these, 31% were more than 65 years of age, 9.5% were Indigenous Australians, 4.3% were pregnant and 77% had chronic co-morbidities. Influenza B was detected in 30% of patients. Vaccination coverage was estimated at 81% in patients more than 65 years of age but only 49% in patients aged less than 65 years with chronic comorbidities. Vaccination effectiveness against hospitalisation with influenza was estimated at 50% (95% confidence interval: 33%, 63%, P<0.001). We detected a significant number of hospital admissions with confirmed influenza in a national observational study. Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. Our results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza in the 2013 season. This work i